SUMMARY The genital mycoplasmas represent a complex and unique group of microorganisms that have been associated with a wide array of infectious diseases in adults and infants. The lack of conclusive knowledge regarding the pathogenic potential of Mycoplasma and Ureaplasma spp. in many conditions is due to a general unfamiliarity of physicians and microbiology laboratories with their fastidious growth requirements, leading to difficulty in their detection; their high prevalence in healthy persons; the poor design of research studies attempting to base association with disease on the mere presence of the organisms in the lower urogenital tract; the failure to consider multifactorial aspects of diseases; and considering these genital mycoplasmas only as a last resort. The situation is now changing because of a greater appreciation of the genital mycoplasmas as perinatal pathogens and improvements in laboratory detection, particularly with regard to the development of powerful molecular nucleic acid amplification tests. This review summarizes the epidemiology of genital mycoplasmas as causes of neonatal infections and premature birth; evidence linking ureaplasmas with bronchopulmonary dysplasia; recent changes in the taxonomy of the genus Ureaplasma; the neonatal host response to mycoplasma and ureaplasma infections; advances in laboratory detection, including molecular methods; and therapeutic considerations for treatment of systemic diseases.

Objective To test the hypothesis that heart rate characteristics (HRC) monitoring improves neonatal outcomes. Study design Two-group, parallel, individually randomized controlled clinical trial of 3003 very low birth weight infants in 9 NICUs. In one group, HRC monitoring was displayed; in the other, it was masked. The primary outcome was number of days alive and ventilator-free in the 120 days after randomization. Secondary outcomes were mortality, number of ventilator days, NICU stay and antibiotic use. Results Mortality was reduced in infants whose HRC monitoring was displayed, from 10.2% to 8.1% (HR = 0.78, 95% CI = 0.61 to 0.99, P = 0.04, number needed to monitor 48), and there was a trend toward increased days alive and ventilator-free (95.9 of 120 days compared to 93.6 in controls, P = 0.08). Mortality benefit was concentrated in infants with birth weight <1000g (HR=0.74, 95% CI 0.57 to 0.95, P=0.02, number needed to monitor 23). There were no significant differences in the other outcomes. Conclusion Heart rate characteristics monitoring can reduce mortality in very low birth weight infants.

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To gain insight into the mechanisms that regulate the development of the H chain CDR3 (CDR-H3), we used the scheme of Hardy to sort mouse bone marrow B lineage cells into progenitor, immature, and mature B cell fractions, and then performed sequence analysis on VH7183-containing Cμ transcripts. The essential architecture of the CDR-H3 repertoire observed in the mature B cell fraction F was already established in the early pre-B cell fraction C. These architectural features include VH gene segment use preference, DH family usage, JH rank order, predicted structures of the CDR-H3 base and loop, and the amino acid composition and average hydrophobicity of the CDR-H3 loop. With development, the repertoire was focused by eliminating outliers to what appears to be a preferred repertoire in terms of length, amino acid composition, and average hydrophobicity. Unlike humans, the average length of CDR-H3 increased during development. The majority of this increase came from enhanced preservation of JH sequence. This was associated with an increase in the prevalence of tyrosine. With an accompanying increase in glycine, a shift in hydrophobicity was observed in the CDR-H3 loop from near neutral in fraction C (−0.08 ± 0.03) to mild hydrophilic in fraction F (−0.17 ± 0.02). Fundamental constraints on the sequence and structure of CDR-H3 are thus established before surface IgM expression.

BackgroundExtracorporeal membrane oxygenation (ECMO) is a life-saving support system used in neonates and young children with severe cardiorespiratory failure. Although ECMO has reduced mortality in these critically-ill patients, almost all patients treated with ECMO develop a systemic inflammatory response syndrome (SIRS) characterized by a ‘cytokine storm’, leukocyte activation, and multisystem organ dysfunction. We used a neonatal porcine model of ECMO to investigate whether rising plasma concentrations of inflammatory cytokines during ECMO reflect de novo synthesis of these mediators in inflamed tissues, and therefore, can be used to assess the severity of ECMO-related SIRS.MethodsThree-week-old previously-healthy piglets were subjected to venoarterial ECMO for up to 8 hours. SIRS was assessed by histopathological analysis, measurement of neutrophil activation (flow cytometry), plasma cytokine concentrations (enzyme immunoassays), and tissue expression of inflammatory genes (polymerase chain reaction/western blots). Mast cell degranulation was investigated by measurement of plasma tryptase activity.ResultsPorcine neonatal ECMO was associated with systemic inflammatory changes similar to those seen in human neonates. TNF-α and interleukin-8 (IL-8) concentrations rose rapidly during the first 2 hours of ECMO, faster than the tissue expression of these cytokines. ECMO was associated with increased plasma mast cell tryptase activity, indicating that increased plasma concentrations of inflammatory cytokines during ECMO may result from mast cell degranulation and associated release of preformed cytokines stored in mast cells.ConclusionsTNF-α and IL-8 concentrations rose faster in plasma than in the peripheral tissues during ECMO, indicating that rising plasma levels of these cytokines immediately following the initiation of ECMO may not reflect increasing tissue synthesis of these cytokines. Mobilization of preformed cellular stores of inflammatory cytokines such as in mucosal mast cells may play an important pathophysiological role in ECMO-related SIRS.

Tyrosine and glycine constitute 40% of complementarity determining region 3 of the immunoglobulin heavy chain (CDR-H3), the center of the classic antigen-binding site. To assess the role of DH RF1-encoded tyrosine and glycine in regulating CDR-H3 content and potentially influencing B cell function, we created mice limited to a single DH encoding asparagine, histidine, and arginines in RF1. Tyrosine and glycine content in CDR-H3 was halved. Bone marrow and spleen mature B cell and peritoneal cavity B-1 cell numbers were also halved, whereas marginal zone B cell numbers increased. Serum immunoglobulin G subclass levels and antibody titers to T-dependent and T-independent antigens all declined. Thus, violation of the conserved preference for tyrosine and glycine in DH RF1 alters CDR-H3 content and impairs B cell development and antibody production.

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Background Abnormal heart rate characteristics (HRC) wax and wane in early stages of culture-positive, late-onset septicemia (LOS) in patients in the neonatal intensive care unit (NICU). Continuously monitoring an HRC index leads to a reduction in mortality among very low birth weight (VLBW) infants. We hypothesized that the reduction in mortality was due to a decrease in septicemia-associated mortality. Methods This is a secondary analysis of clinical and HRC data from 2989 VLBW infants enrolled in a randomized controlled trial of HRC monitoring in 9 NICUs from 2004–2010. Results LOS was diagnosed 974 times in 700 patients, and the incidence and distribution of organisms were similar in HRC display and non-display groups. Mortality within 30 days of LOS was lower in the HRC display compared to the non-display group (11.8% vs 19.6%, RR 0.61, 95% CI 0.43, 0.87, p<0.01), but mortality reduction was not statistically significant for patients without LOS. There were fewer large, abrupt increases in the HRC index in the days leading up to LOS diagnosis in infants whose HRC index was displayed. Conclusions Continuous HRC monitoring is associated with a lower septicemia-associated mortality in VLBW infants, possibly due to diagnosis earlier in the course of illness.